Utilization of the 10B(n, Alpha)7Li reaction for Neutron Capture Therapy (NCT) provides potentially optimal conditions for radiotherapy. Physiological localization of boron in tumor permits selective irradiation of cancer cells within the radiation field, as the range of the He and Li ions is about one cell diameter (about 10Mu). Furthermore, these charged particles should provide a therapeutic gain generally accorded to radiation of high linear energy transfer. Cell-level targeting of radiotoxicity from 10B carried by cell-specific antibodies therefore appears possible with NCT. Boronated compounds available to date for NCT are not tumor specific, and boron concentrations in blood and other background tissues remain high. We propose to investigate the use of boronated dextran-antibody complexes as vehicles for the transport f 10B to tumors. We plan to develop conjugates suitable for treatment of human melanomas by the combination of previously demonstrated techniques. Dextran bridges have been shown to afford additional carrying capacity as well as water solubility for drug-antibody conjugates as a consequence of multiple drug attachment sites and hydrophilic groups on the polysaccharide molecule. We expect that 10B concentrations adequate for therapy will be available at dextran-antibody conjugation levels which have shown retention of solubility and anti-tumor activity. Using monoclonal antibodies to human melanomas already developed by one of us (SF), we intend first to test the efficacy of NCT employing boronated dextran-antibody complexes against cell lines derived from human melanomas growing in cell culture and in athymic "nude" mice. If successful, this will be followed by trials of NCT using antibodies targeted to human melanoma tissue obtained from surgical biopsies when these are grown in "nude" mice. Although the ultimate goal is therapy of cancer in human beings, clinical treatment is not part of this research plan. This work, however, should establish the feasibility of antibody-directed 10B NCT in man, both for tumor therapy and by extension of the underlying principles--for radiation inactivation of other cellular targets toward which appropriately selective antibodies can be developed.